SummaryDexamethasone releasing PLGA poly(lactic-co-glycolic acid) microsphere/PVA (polyvinyl alcohol) hydrogel composite coatings have been shown to prevent the foreign body response (FBR) to subcutaneous (SC) implants in a rat model1. It was previously reported that this dose was ineffective in preventing FBR in Gottingen minipigs, Moreover, increasing the dexamethasone dose while keeping the same release profile did not prevent FBR2. The objective of the present study was to optimize the dexamethasone release kinetics by altering the physical properties of the PLGA microspheres. When lower molecular weight PLGA was used (12 instead of 25 kDa), fibrosis was not observed up to 14 days (previously had been observed by day 7). This was a significant breakthrough in preclinical testing of our composite coatings in a large animal model, paving the way for clinical studies.